The purpose of the proposed research is to study the mechanism(s) of virus persistence in cultured human cells by the human enterovirus, echovirus 6. The specific aims of this project are to determie whether: 1) virus mutations occur during a persistent eterovirus infection, 2) incomplete synthesis or aberrant post- translational processing of viral proteins occur during persistent infections, 3) cellular factors are involved in virus persistence, 4) defective viruses or their genomes play a role in persistent infections, and 5) echovirus 6 persistence can be established in cultures of differentiated human cells. These aims will be approached by: 1) isolation of viruses produced by persistently infected cells, 2) use of molecular cloning techniques to compare and analyze the viral RNA genomes in acutely and persistently infected cells, 3) compare synthesis and processing of viral and cellular proteins in acute and persistent infections, 4) curing cells of virus and comparison of the cured cells to parental cells, 5) investigation of the stage of standard virus infection which is inhibited during persistent infection, 6) investigation of the ability of viral RNA from persistently infected cells to transfect uninfected parental cells and confer persistent infection, and 7) examination of a variety of human cells that can be persistently infected by an enterovirus. The enterovirus, used for these studies, causes persistent infection in humans and can produce prigressive encephalitis and paralysis in agammaglobulinemics. Since in vivo systems are difficult to analzye, an in vitro system is important for study of virus persitence and will provide useful information for understanding events that lead to viral neurological diseases processes in immunologically compromised patients.